We report three cases of adenomyoepithelioma of the breast that occurred in middle aged women. The tumor is characterized by a balanced proliferation of epithelial tubules and surrounding myoepithelial cells that are spindle shaped or have clear cytoplasms. The first case mimicked tubular adenoma in the initial biopsy. However, on excision it turned out to be an adenomyoepithelioma of the tubular. The other two cases were lobulated types and had fibroadenomatous areas. The morphologic appearance of this tumor varies, making it misleading to other benign or even malignant lesions. The tumor has a potential for local recurrence, therefore, wide excision is recommended for proper diagnosis and treatment.
Adult ; Breast Neoplasms/metabolism/*pathology ; Carcinoma, Adenoid Cystic/metabolism/*pathology ; Case Report ; Diagnosis, Differential ; Female ; Human ; Immunohistochemistry ; Middle Age

OBJECTIVETo investigate the effect of transforming growth factor-beta1 (TGF-beta1) on EDA region of fibronectin in oral squamous cell carcinoma and adenoid cystic carcinoma cells.

METHODSImmunohistochemistry and reverse transcription polymerase chain reaction technique were used to detect the changes of EDA proteins and mRNAs expression.

RESULTSThe immunostaining ratio in Tca83 cells with TGF-beta1 was greatly higher than that in Tca83 cells without TGF-beta1 (P < 0.01), the immunostaining ratio in SACC-83 cells with TGF-beta1 was higher than that in SACC-83 cells without TGF-beta1 (P < 0.05), but there was no significant difference between SACC-LM cells with TGF-beta1 and SACC-LM cells without TGF-beta1 (P > 0.05). In the three oral carcinoma cells, the expression of EDA(+) mRNAs in the group with TGF-beta1 was higher than that in the group without TGF-beta1 (P < 0.05). The expression of EDA(-) mRNAs in the group with TGF-beta1 was lower than that in the group without TGF-beta1 (P < 0.05).

CONCLUSIONSTGF-beta1 could influence EDA region splicings and upregulate the expression of EDA region in Tca83, SACC-83 and SACC-LM cells, and might play an important role in accelerating oral carcinoma cells adhesion and tumor invasion and metastasis.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Fibronectins ; metabolism ; Humans ; Mouth Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Transforming Growth Factor beta1 ; pharmacology

OBJECTIVETo evaluate the expression of nuclear factor kappa B (NF-kappaB) p65 in relation to angiogenesis microvessel density (MVD) and clinical outcomes in adenoid cystic carcinoma of salivary glands (ACCs).

METHODSImmunohistochemical staining method was used to quantify the protein expression levels of NF-kappaB p65 in 80 surgically resected salivary gland ACC and normal salivary tissues. In all cases of ACCs, microvessel density was evaluated by counting any CD(34)-reactive endothelial cell or endothelial-cell cluster. The patients with ACCs were followed up from 1992 to 2002.

RESULTSNF-kappaB p65 was detected in the cytoplasm of normal and ACC cells, but was only in the nucleus of tumor cells; while there was no NF-kappaB p65 nuclear staining in all the controls. The mean value of MVD was (47.07 +/- 13.44), which had significant correlations with NF-kappaB p65 expression (P < 0.01). In three histological types of salivary gland ACC, the expressions of NF-kappaB and MVD were significantly higher in solid type than in cribriform type and tubular type (P < 0.01). NF-kappaB p65 expression and MVD were significantly correlated to clinical stage, tumor size, perineural and vascular invasion, recurrence and metastasis (P < 0.05), but there were no correlations between those three factors and patient age, gender and tumor site (P > 0.05). Multivariate analysis showed NF-kappaB (P < 0.05) expression, MVD (P < 0.01), histotypes (P < 0.01), and perineural invasion (P < 0.05) had an independent prognostic impact on overall survival.

CONCLUSIONSThe expression of NF-kappaB p65 was related to MVD, and the correlation between those two factors and clinico-pathological factors and prognosis of ACCs are significant.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Prognosis ; Salivary Gland Neoplasms ; metabolism ; pathology ; Transcription Factor RelA ; metabolism

OBJECTIVETo determine the effect of tyrosine kinase A (TrkA) and vascular endothelial growth factor receptor 2 (VEGFR2) in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC).

METHODSThe expression of TrkA and VEGFR2 were detected by immunohistochemical staining in 47 cases of SACC of salivary glands. Clinical data were reviewed by multivariate prognostic analysis.

RESULTSThe positive rate of TrkA and VEGFR2 in SACC was 87.23% (41/47) and 85.11% (40/47) respectively. Express of TrkA and VEGFR2 in perineural invasion and recurrence group were higher than non-perineural invasion and non-recurrence group. Significant difference was found in microvessel density (MVD) and VEGFR2 expression within different groups (P < 0.05). MVD in perineural invasion group (25.14 +/- 2.83) was significantly higher than that in none perineural invasion group (18.81 +/- 1.33) (P < 0.05). MVD in recurrence or metastasis group (26.58 +/- 2.38) was significantly higher than that (19.06 +/- 1.39) in none recurrence nor metastasis group (P < 0.05).

CONCLUSIONPositive correlation between expression of TrkA, VEGFR2 and nerve invasion and vessel metastasis of SACC indicate that TrkA and VEGFR2 play important roles in the invasion and metastasis of SACC. It is possible that TrkA and VEGFR2 could be an aid for evaluating the prognosis of SACC patients.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Humans ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Receptor, trkA ; metabolism ; Salivary Gland Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor Receptor-2

OBJECTIVETo observe the expression of Schwann cell marker GFAP and myoepithelial cell marker alpha-SMA in salivary adenoid cystic carcinoma (ACC), and to evaluate the relationship of GFAP, alpha-SMA and perineural invasion in ACC.

METHODSImmunohistochemical SABC method, double-label immunofluorescence and CLSM were used to detect the expression of GFAP and alpha-SMA proteins in salivary ACC tissue samples.

RESULTSIn salivary ACC tissue samples, both GFAP and alpha-SMA proteins were positive, which were coexpressed in cytoplasm of the same onco-myoepithelial cells.

CONCLUSIONSThere may be Schwann cell differentiation in onco-myoepithelial cell of salivary ACC, and it may be the pathological base of perineural invasion in salivary ACC.

Actins ; metabolism ; Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Epithelial Cells ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Muscle Cells ; metabolism ; pathology ; Salivary Gland Neoplasms ; metabolism ; pathology ; Schwann Cells ; metabolism ; pathology

OBJECTIVEThis study aimed to investigate the expression of midkine (MK) and microvessel density (MVD) in patients with salivary adenoid cystic carcinoma (SACC) and its clinical significance, as well as detect the correlation between the expression of MK and MVD in SACC.

METHODSImmunohistochemistry analysis (SP method) for MK and MVD were performed on 60 cases of SACC and 26 cases of normal salivary gland tissue. The expression of MK and MVD, as well as the correlation between the expression of MK and MVD in SACC were detected.

RESULTSIn SACC, the MK expression rate was 70.0% (42/60), and MK was not expressed in normal tissue. Statistical significance was found between SACC and normal tissue (P<0.05). The MVD values in SACC and normal salivary gland tissues were 38.73 +/- 8.96 and 11.15 +/- 3.33, respectively. These values were statistically significant (P<0.05). The expression levels of MK and MVD were unrelated to age, gender, and type in SACC (P>0.05), but correlated with tumor size, lymph node metastasis, and tumor-node-metastasis in SACC (P<0.05). The expression of MK and MVD was positively correlated with SACC (r=0.560, P<0.05).

CONCLUSIONSACC is correlated with the expression of MK protein and the increase in MVD, which may be some of the early diagnostic markers in SACC.

Carcinoma, Adenoid Cystic ; enzymology ; pathology ; Cytokines ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Microvessels ; Nerve Growth Factors ; Salivary Gland Neoplasms ; enzymology ; pathology ; Salivary Glands ; enzymology

Interferon-γ (IFN-γ), a key effector molecule in anti-tumor immune response, has been well documented to correlate with the intratumoral infiltration of immune cells. Of interest, however, a high level of IFN-γ has been reported in salivary adenoid cystic carcinoma (SACC), which is actually a type of immunologically cold cancer with few infiltrated immune cells. Investigating the functional significance of IFN-γ in SACC would help to explain such a paradoxical phenomenon. In the present study, we revealed that, compared to oral squamous cell carcinoma cells (a type of immunologically hot cancer), SACC cells were less sensitive to the growth-inhibition effect of IFN-γ. Moreover, the migration and invasion abilities of SACC cells were obviously enhanced upon IFN-γ treatment. In addition, our results revealed that exposure to IFN-γ significantly up-regulated the level of programmed death ligand 1 (PD-L1) on SACC cell-derived small extracellular vesicles (sEVs), which subsequently induced the apoptosis of CD8⁺ T cells through antagonizing PD-1. Importantly, it was also found that SACC patients with higher levels of plasma IFN-γ also had higher levels of circulating sEVs that carried PD-L1 on their surface. Our study unveils a mechanism that IFN-γ induces immunosuppression in SACC via sEV PD-L1, which would account for the scarce immune cell infiltration and insensitivity to immunotherapy.
B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/pathology* ; Carcinoma, Adenoid Cystic/pathology* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Humans ; Immunosuppression Therapy ; Interferon-gamma/pharmacology* ; Mouth Neoplasms/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Salivary Gland Neoplasms/pathology*

Adult ; Breast Neoplasms ; metabolism ; pathology ; secondary ; Carcinoid Tumor ; metabolism ; pathology ; surgery ; Carcinoma, Adenoid Cystic ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hysterectomy ; Keratins ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; metabolism ; pathology ; Sex Cord-Gonadal Stromal Tumors ; metabolism ; pathology ; Synaptophysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo assess the epidermal growth factor receptor (EGFR) status in salivary adenoid cystic carcinoma and explore its role in cancer invasion.

METHODSFifty-four patients with pathologically confirmed salivary adenoid cystic carcinoma (SACC) were divided into invasion group and non-invasion group. The EGFR expression was determined by immunohistochemstry (SP staining). The relations between the EGFR expression and the SACC clinical pathological characteristics were analyzed.

RESULTSEGFR were mainly expressed in the cell membrane and cytoplasm in the tissue of SACC. The positive rate of EGFR expression in the tumor tissue was 75.9% (41/54), and EGFR was over-expressed in the cytoplasm. The positive rate of EGFR expression in invasion group was higher than that in the non-invasion group (10.0%, P < 0.05). EGFR expression were related with the SACC T stages, histological types, distant metastasis, lymph node metastasis, and nerve invasion (P < 0.05).

CONCLUSIONSA higher expression of EGFR gene in the cytoplasm may have important effect on the progression of invasive carcinoma. Further investigations are required to develop new strategy in the treatment of salivary adenoid cystic carcinoma.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Cell Membrane ; metabolism ; Cytoplasm ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Receptor, Epidermal Growth Factor ; metabolism ; Salivary Gland Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression of Pin1, beta-catenin and cyclin D1 in salivary adenoid cystic carcinomas (SACC) and to evaluate the role of beta-catenin and Pin1 in SACC carcinogenesis.

METHODSThe expressions of Pin1, beta-catenin and cyclin D1 were examined in the specimens of 65 patients with SACC by immunohistochemistry, and Pin1 protein and mRNA expressions detected by Western blot and RT-PCR in four SACC cell lines.

RESULTSPin1 was overexpressed in 51 cases of ACC (78%), and 41 (63%) cases showed positive immunoreactivity for cyclin D1 protein in the nuclear fraction in tumor tissues. Fourteen (22%) cases showed positive immunoreactivity for beta-catenin protein in the nuclear/cytoplasmic fraction in tumor tissues, 6 of which exhibited quite evident expression of beta-catenin in nucleolus. The expression of membranous beta-catenin was down-regulated in most of the patients with lymph node metastasis (11/14).

CONCLUSIONSThe results suggest that Pin1 and beta-catenin signalling pathway were activated in SACC and might play a pivotal role in SACC carcinogenesis and metastasis.

Carcinoma, Adenoid Cystic ; metabolism ; pathology ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Humans ; Lymphatic Metastasis ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasm Invasiveness ; Peptidylprolyl Isomerase ; metabolism ; Salivary Gland Neoplasms ; metabolism ; pathology ; beta Catenin ; metabolism